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Thapsigargin inhibits a potassium conductance and stimulates calcium influx in the intact rat lens
Author(s) -
Thomas Grégoire R.,
Sanderson Julie,
Duncan George
Publication year - 1999
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1999.191ab.x
Subject(s) - thapsigargin , depolarization , biophysics , chemistry , conductance , calcium , membrane potential , tetraethylammonium , endoplasmic reticulum , potassium , endocrinology , biochemistry , biology , mathematics , organic chemistry , combinatorics
1 An increase in lens cell calcium has long been associated with cortical cataract. Recently, it has been shown that thapsigargin induces a rise in lens cell calcium by release from endoplasmic reticulum stores. The effects of this rise on the optical and membrane characteristics of the lens were studied in the isolated rat lens. 2 The electrical characteristics of the isolated, perifused rat lens were measured using a two‐internal microelectrode technique that permits measurement of plasma membrane conductance ( G m ), membrane potential ( V m ) and junctional conductance in the intact lens. 3 Thapsigargin (1 μM) induced a rapid overall depolarization of V m that was accompanied by first a decrease and then an increase in G m . 4 Replacing external Na + with tetraethylammonium (TEA) abolished the decrease in G m . However, a transient increase phase was still observed. 5 The changes in conductance were further characterized by measuring 22 Na + and 45 Ca 2+ influxes into the isolated lens. Thapsigargin (1 μM) induced a transient increase in 45 Ca 2+ , but did not affect Na + influx. 6 The Ca 2+ channel blocker La 3+ (10 μM) totally inhibited the thapsigargin‐induced Ca 2+ influx. It also blocked the increase in G m observed in control and in Na + ‐free‐TEA medium. In the absence of external calcium, thapsigargin induced a small depolarization in V m . 7 These data indicate that thapsigargin induces both a decrease in K + conductance and an increase in Ca 2+ conductance. These probably result from release of stored Ca 2+ and subsequent activation of store‐operated Ca 2+ channels (capacitative Ca 2+ entry). 8 Thapsigargin application over the time course of these experiments (24 h) had no effect on junctional conductance or on the transparency of the lens.